Abstract

The application of terahertz pulsed spectroscopy within the US Food and Drug Administration's (FDA's) recent process analytical technology (PAT) initiative is considered. As a case study the potency levels in paracetamol (4–acetamidophenol) and aspirin (acetylsalicylic acid) test tablets have been recovered from the terahertz absorption spectra using a multivariate partial–least–squares (PLS) calibration model. Root–mean–square errors of cross–validation (RMSECVs) of 2.85% and 3.90% were obtained for paracetamol and aspirin, respectively. Information about other excipients can also be obtained; for example, using the strong lactose absorption lines in the tablets, RMSECVs of 3.65% and 4.30% could be recovered from the paracetamol and aspirin samples, respectively. As active ingredients may also change their solid–state form during formulation processing or storage and as this can adversely affect the final dosage performance, monitoring of pharmaceutical ingredients is essential for a ‘right–first–time’ philosophy within the industry. Terahertz pulse spectroscopy is a high–throughput technique with many areas of potential exploitation in the pharmaceutical industry; these issues are discussed in this paper.